In phase II we propose an experimental plan that will lead to a commercial quality electrospray/photoionization (ES/PI) source. We plan to: (i) optimize and build a pre-commercial prototype ES/PI source for use on commercial mass spectrometers, and (ii) develop and demonstrate key applications that highlight the unique benefits of the ES/PI source, The goals of the phase I project were met and a prototype ES/PI was built and tested on a Micromass LCT and an Agilent MSD mass spectrometer. Since phase I, Syagen has performed additional tests, and has adapted a new source to a Waters ZQ. The ES/PI performance was measured as a function of flow rate, heating, PI position, and ES ionization (ESI) voltage. Tests were conducted using a variety of compounds not ionized efficiently by ESI (e.g., steroids, phenols, aldehydes, etc.). PI ionized these compounds efficiently. Further tests were performed on drug and protein mixtures to examine the potential to analyze both classes of compounds simultaneously. The significance and importance of this work is high. Developing new ionization sources for life science research is a major thrust in mass spectrometry as witnessed by the awarding of the 2002 Nobel Prize for ESI and laser desorption/ionization (e.g., MALDI) of biological molecules. This proposed work will greatly expand the capabilities of ESI making possible the development of new advanced methods for high-throughput analysis. There is already interest in this technology by commercial MS vendors. If we are successful with the phase II work, we are confident of finding a commercialization partner for the ES/PI source.